We propose to construct human partial trisomy 21 neuronal cell lines which can be differentiated and maintained for several months while expressing a credible neuronal phenotype with assembled neurofilaments and an extensive dendritic arbor. Partial trisomy 21 is the cause of Down's syndrome and Down's syndrome patients show numerous symptoms of accelerated aging including the percocious development of lesions characteristic of Senile Dementia of the Alzheimer Type (SDAT). If these partial trisomy 21 neuronal cells can be induced to develop SDAT pathology such as paired helical filaments (PHF) at an accelerated pace (relative to control cell lines), then these cells and this approach may be an extremely useful tool for elucidating the pathogenesis and possibly the etiology of SDAT. Manifestations of SDAT pathology in a human neuronal cell line could, in and of itself, provide a convenient tool in the search for effective therapeutic interventions. This is an innovative high risk pilot project.